Cardiotoxicity of immune checkpoint inhibitors
Gilda Varricchi,Maria Rosaria Galdiero,Giancarlo Marone,Gjada Criscuolo,Maria Triassi,Domenico Bonaduce,Gianni Marone,Carlo G. Tocchetti +7 more
- Vol. 2, Iss: 4
TLDR
The mechanisms of the most prominent checkpoint inhibitors are described, specifically ipilimumab (anti-CTLA-4, the godfather of checkpoint inhibitors) patient and monoclonal antibodies targeting PD-1 and PD-L1 (eg, atezolizumab).Abstract:
Cardiac toxicity after conventional antineoplastic drugs (eg, anthracyclines) has historically been a relevant issue. In addition, targeted therapies and biological molecules can also induce cardiotoxicity. Immune checkpoint inhibitors are a novel class of anticancer drugs, distinct from targeted or tumour type-specific therapies. Cancer immunotherapy with immune checkpoint blockers (ie, monoclonal antibodies targeting cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), programmed cell death 1 (PD-1) and its ligand (PD-L1)) has revolutionised the management of a wide variety of malignancies endowed with poor prognosis. These inhibitors unleash antitumour immunity, mediate cancer regression and improve the survival in a percentage of patients with different types of malignancies, but can also produce a wide spectrum of immune-related adverse events. Interestingly, PD-1 and PD-L1 are expressed in rodent and human cardiomyocytes, and early animal studies have demonstrated that CTLA-4 and PD-1 deletion can cause autoimmune myocarditis. Cardiac toxicity has largely been underestimated in recent reviews of toxicity of checkpoint inhibitors, but during the last years several cases of myocarditis and fatal heart failure have been reported in patients treated with checkpoint inhibitors alone and in combination. Here we describe the mechanisms of the most prominent checkpoint inhibitors, specifically ipilimumab (anti-CTLA-4, the godfather of checkpoint inhibitors) patient and monoclonal antibodies targeting PD-1 (eg, nivolumab, pembrolizumab) and PD-L1 (eg, atezolizumab). We also discuss what is known and what needs to be done about cardiotoxicity of checkpoint inhibitors in patients with cancer. Severe cardiovascular effects associated with checkpoint blockade introduce important issues for oncologists, cardiologists and immunologists.read more
Citations
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Targeting Oncoimmune Drivers of Cancer Metastasis.
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Immune checkpoint inhibitor-induced takotsubo syndrome and diabetic ketoacidosis: rare reactions.
TL;DR: In this paper, a case report identifies a patient presenting with takotsubo syndrome followed by ketoacidosis (associated with sodium-glucose transport protein 2 (SGLT2) inhibitor) in the setting of combination ipilimumab and nivolumab therapy for metastatic melanoma.
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Incidence of Cardiovascular Events in Patients Treated With Immune Checkpoint Inhibitors
Dorien Laenens,Yuling Yu,Béatrice Santens,Johanna Jacobs,R. Beuselinck,Oliver Bechter,Els Wauters,Jan A. Staessen,Stefan Janssens,Lucas Van Aelst +9 more
TL;DR: Cardiovascular events during and after ICI treatment are more common than currently appreciated, and compared with matched cancer and population controls, MACE incidence rates are significantly higher, suggesting a potential harmful effect ofICI treatment besides the underlying risk.
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A Systematic Review of the Mechanisms Involved in Immune Checkpoint Inhibitors Cardiotoxicity and Challenges to Improve Clinical Safety
Néstor Rubio-Infante,Yoel A. Ramírez‐Flores,Elena C. Castillo,Omar Lozano,Gerardo García-Rivas,Guillermo Torre-Amione +5 more
TL;DR: It is proposed that self-antigens released from cardiac tissues or cancer cells and the severity/advancement of cancer disease have an important role in ICI cardiotoxicity.
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